经纹状体注射胶质细胞系源性神经营养因子对帕金森病模型小鼠黑质多巴胺能神经元保护作用的实验研究

目的 研究经纹状体注射胶质细胞系源性神经营养因子（glial cell line-derived neumtrophic factor，GDNF）对帕金森病（Parklnson disease，PD）模型小鼠中脑黑质多巴胺能神经元的保护作用。方法 利用1-甲基-4-苯基1，2，3，6-四氢吡啶（1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine，MPTP）制备成年小鼠PD模型，通过单侧纹状体定位注射GDNF，取中脑黑质节段，做连续冠状石蜡切片，结合免疫组织化学染色方法，观察各组酪氨酸羟化酶（tyrosine hydroxylase，TH）、钙结合蛋白（calbindin D28k，CB）的表达，光镜观察并细胞计数，统计学分析。结果 在模型制备的第4,6天，单侧纹状体定位注射GDNF后，小鼠黑质致密部TH与CB阳性神经元数量显著多于注射PBS组。结论 经纹状体注射GDNF对成年PD小鼠黑质多巴胺能神经元具有保护作用，且这种保护作用可能与细胞内CB表达增加有关。

The protective effect of intrastriatal GDNF on the dopaminergic neurons in Parkinson disease mice

Objective To investigate the protective effect of intrastriatal GDNF on dopaminergic(DA) neurons in the substantia nigra of MPTP-induced mouse model of Parkinson disease(PD).Methods The PD model was established in adult KM mice four or six days after an intraperitoneal injection of MPTP 30 mg/kg.The model mice were then treated by giving GDNF into the striatum.After a seven-day survival period,the model mice were sacrificed to get the segment of substantial nigra(SN) fixed,embedded and coronally sectioned continuously.The microsections were processed by immunohistochemistry using anti-TH and anti-CB antibodies to label DA neurons and CB-containing neurons respectively,which were counted under microscope and analyzed statistically.Results Seven days after the steriotaxic intrastriatal injection of GDNF,the numbers of TH and CB positive neurons were found significantly higher than that in the untreated model mouse control group.Conclusion Intrastriatal GDNF can protect DA neurons in PD model mice,and this role may be related to the increase of CB expression.